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Tuesday, April 30, 2013

We had a good friend come up to visit recently (congrats to him on accepting a position with Intel). We took the Little Bear out and explored the Museum of Vertebrate Zoology at UC Berkeley's Cal Day. Of course I had to show off the dinosaur skeletons in my building. The Tyrannosaurus is always a big hit at capturing imaginations.

In awe of the Tyrannosaurus.

There were several exhibits, and even some live specimens to interact with:

Fearlessly, but cautiously, examining the boa

While touring the Museum, the Little Bear made a comment that I am so very proud of. We were looking at the fossils of several marine mammals. I was describing the anatomy of the whale, and the Little Bear interrupted me to point at this part and tell me that it was the "hand". Yes! What a very clever observation, dear little person!

Whale "hand"

Of course, being the big nerd that I am, I then held up both her hand and my hand next to it, and explained how the bones in the whale's flipper are actually homologous (shared from a common ancestor) with human hand bones. (I might have also used the words metacarpals and phalanges... but really, how are children supposed to learn if we are afraid to challenge them with new words and ideas? Lucky for me, she just eats it up.) So, I told her, even though a whale's flipper, and a human hand look quite different on the outside, the bones underneath enlighten us about our shared evolutionary history.

She was able to recognize, at two years old, what so many people close their eyes to. Amazing.

Friday, April 26, 2013

It's strange to think that my Little Bear has friends (not just kids she tolerates because we make them play together). She is truly excited to see certain kids, and does a significantly better job of sharing and playing nicely with them than with other children.

The Little Bear likes having someone younger than her
(J is almost one year younger exactly) to play with.

One of her friends is J, who reminds me exactly of the Little Bear every time I see her (they are both spunky, smart, and full of personality). After a couple rough visits, J and Little Bear played together wonderfully. This weekend, the Little Bear told me, "Mommy, I'll be right back. I'm going to go get J." Melt!

Playing tetherball with her best friend, M.

Her other friend is M. They've been in daycare together since Little Bear was about 6 months old (so for 3/4 of their lives). When I came into the playground area at daycare yesterday, all of the little kids were playing together, except for these two. I looked around, and at the inside area, I see M, with his shoes off, walking around. Next to M's shoes, I see Little Bear's shoes. About that time, M spots me. As he ran towards me for a hug, Little Bear popped her head out from around the corner to squeal then run away. It cracks me up that they are partners in crime, already.

It is bittersweet that both of her best friends (and their parents!) have recently moved away (one to San Francisco, and one to Irvine). But, I am very excited that it will give us wonderful opportunities to visit places we haven't seen. I don't know where we'll be headed in the next year or so, but I do know that we'll have wonderful friends all over the world. I hope the same will be true for the Little Bear.

Thursday, April 25, 2013

Tips for science blogging from Holly Dunsworth (read the full interview on her interview about Social Media for Science here):

It’s not for everyone, but everyone should appreciate the myriad reasons for why it’s done.

Be social. If you blog, you need to be on Facebook and Twitter to share your posts.

Reciprocate. If you want people to share your work, you need to share theirs.

Have patience. If dialogue is what you want, it’s going to take a lot of work and a lot of time.

Do it. If you don’t enjoy it, then stop doing it.

I am definitely taking these tips to heart. I do need to expand my social network to other scientists who blog/share about science. I am primarily a scientist, and I actually like doing research, I am not as social as I could be, if blogging/science communication were my full-time job. I find that it is especially difficult for me to keep up with Twitter.

Lol, the patience is no problem. Submitting papers, and waiting for reviews, has helped me learn patience very well.

The one that resonates the most with me is the last bit. I love talking with people about science, and things that I find fascinating. Blogging is a great way to share science more broadly. For me though, it is personally important because it motivates me: 1)to find the words to explain my interests in common language; and, 2) to learn more details about the research that interests me so that I can explain it to others.

There was recently a hubbub about the National Science Foundation (NSF) funding a grant to study snail sex to Maurine Neiman, John Logsdon, and Jeffrey Boore. Because, y'know, snails are so slimy, and sex is gross, so that makes snail sex... icky, and what is it good for?!?

The work has been justified time and again (specifically see this response). I have complete confidence in the scientific and academic merit of this work. Here, I'm going to talk about the actual research, focusing on a paper published very recently (see below).

I think we should start by getting to know the snails, and learn two important features of these snails.

Snails?

Yes, snails. This research focuses on a specific type of snail called a New Zealand mud snail (Potamopyrgus antipodarum) that lives in freshwater.

The first interesting bit is that New Zealand mud snails are wonderfully invasive. This means that they are very good at invading a new territory (like a pond), reproducing prolifically to reach very high numbers of individuals, often squeezing out other native snails:

Densities have reached over 300,000 (!) individuals per square meter in the Madison River. - USGS

The second, and arguably more interesting, bit to know is that there are some New Zealand mud snails who always reproduce sexually (with male snails and female snails getting cosy), and some who always reproduce asexually (a process called "parthenogenesis", which basically means that some females produce clones of themselves). Sexual reproduction results in offspring that are a genetic mix of both parents. This combination increases the variation among individuals (for example, you have some features of your mother, and some features from your father, but are not identical to either). Asexual reproduction results in offspring that are nearly identical to the parent. This would be like if instead of being a mix of your parents you were EXACTLY LIKE YOUR MOM. (Please remind me to tell my husband that it could be sooo much worse. Uh, I mean, I love you mom!)

The unique situation with the New Zealand mud snail, with sexual and asexual individuals of the same species, is ideal for investigating how different types of reproduction affect the genome (the set of all a species' DNA), and why, or when, one type might be advantageous over another.

To understand how sexual and asexual reproduction affect the genome, it would be useful to know what the genome looks like. Until recently, however, there were no genome-wide resources for the New Zealand mud snail. Wilton et al., present us with that new resource. They developed reference maps for four mud snail lineages (two sexual, and two asexual). These reference maps are of a subset of the whole genome (called the transcriptome), but contain most of the elements we typically think of as being useful, most notably the coding genes. Now these resources are available for the public to use (and can be accessed here: http://www.biology.uiowa.edu/neiman/transcriptome.php). These resources will greatly assist in studying what the effects of sexual and asexual reproduction are, on a genomic level.

Wednesday, April 24, 2013

I didn't learn much math, and I am a successful scientist because I think critically and found collaborators who were good at math. If you think critically, and find collaborators who are good at mathematics and statistics, you can be a successful scientist without personally knowing much math.

The name of my blog is mathbionerd. I loved math in high school (thanks Mr. Boerner), and majored in Mathematics in college at Creighton University. I did a summer research experience at the University of Nebraska, Lincoln in the Mathematics department. And, for graduate school, I applied to both Mathematics programs and Bioinformatics programs, ultimately choosing the latter, but volunteering to be a teaching assistant for Calculus. I currently study biological questions and large datasets using computer programs and statistical models. So, uh, yes, I think math is important.

Edward Frenkel has an excellent piece responding to Wilson's essay. I completely agree with his conclusion:

"It would be fine if Wilson restricted the article to his personal experience, a career path that is obsolete for a modern student of biology. We could then discuss the real question, which is how to improve our math education and to eradicate the fear of mathematics that he is talking about."

The first thought that struck me, too, about Wilson's essay is that he is giving antiquated advice to modern students. But, the more I thought about it, I realized that the mark he missed is much larger than that. In any field of scientific research, we can gain more insights by taking a different perspective. This perspective may come from collaborators, but truly successful scientists are able to integrate new opinions, and see their own data in new light. Collaborators are very important, but we should be able to critically assess the contributions of our collaborators. Blindly trusting in a mathematician's computations is just as foolish as a mathematician unquestioningly accepting the results of a biological experiment. The roots of scientific inquiry are curiosity and skepticism. Curiosity is developed by what we want to discover, but do not yet know. Skepticism occurs when new data are evaluated, within the context of what we know. The two go hand in hand to result in new, exciting, discoveries. But, being curious without being skeptical makes for poor scientific inquiry.

We become scientists because we are curious. While in training, we learn how to be skeptical by increasing our base knowledge. I cannot imagine a point in my career when that training will end. It can be uncomfortable to be a novice, to admit when we don't understand, and to take the time to learn new material, especially after years of training. But we must, if we are to continue to make progress. This may mean learning more about cardiac disease, or aphid digestion, or polio replication, or linear algebra, or differential equations.

Are there good scientists who are not good at math? Of course there are.

Must one be good at math to be a good scientist? Not necessarily.

But, can anything be gained from perpetuating the notion that math is untouchable, except by experts? No.

Tuesday, April 23, 2013

On Friday I had two papers rejected within a couple hours of each other. Bummer. The good news is that one is rejected with the possibility of resubmission after major revisions, so I'm starting those now. I'm debating what to do with the other, because it was rejected due to lack of interest/space. It may just end up as a blog post (it was a Letter to the Editor).

I also found out that my K99/R00 application was "Not Discussed", which means that it was reviewed, and given comments by NIH reviewers, but did not reach the top 50% threshold to be discussed among the larger committee. Bummer. But, I got the comments today, and I have to say that it really brightened my day! They were generally very positive (thank you, anonymous reviewers!!), and all four reviewers had the same (valid) concern that my fourth aim was too experimental. So, I need to find an experimental biologist to act as my mentor for training for the third component, and then will plan to rewrite and resubmit in July.

Then, today I heard back that the paper written with my undergraduate, and submitted to the peer-reviewed Berkeley Scientific Journal (for undergraduate research) was accepted with minor revision. Wonderful!! It is about phosphatase gene evolution. I'll write it up and feature it here after the revisions are complete.

Monday, April 22, 2013

The first one, "Survival of the Fittest" is the one that is most annoying to me. Why? Because it is often used as a synonym for evolution, but evolution is about so much more!

1. The fittest are not the only ones who survive.

Y'know who survives? The individuals that are sufficient. Sure, some individuals might be more fit than others, and they may have more offspring than others, but many individuals survive (and reproduce) who are certainly not the fittest. And some, who are arguably the fittest, may not survive to reproduce, just due to chance.

2. The term is not specific about the difference between individuals and populations

While the fittest individuals may be more likely to survive to reproduce, they are not, themselves, evolving. New mutations occur in individuals, and individuals are subject to their environment. Yes, selection acts on individuals, but evolution occurs on populations. This point, that populations evolve, not individuals is crucial, and also wildly interesting because things as simple as the size and structure of populations can affect the efficiency of natural selection. For example, natural selection is more efficient in large populations. Alternatively, deleterious mutations are more likely to drift to high frequency in small populations. So, the fitness of individuals is related to the overall population of which they are a member.

3. Evolution isn't all (or likely even primarily) about survival of the fittest

Survival of the fittest is often used to refer specifically to positive selection acting to favor the reproductive success of individuals with higher fitness in their given environment. This term gives the implication that nearly all of evolution is selection acting on mutations. with a beneficial effect Yes, this happens. But, there are other forces at work; two very important ones are:

1. purifying selection, which acts to remove harmful mutations from the population. An extreme example: if a mutation occurs that makes it impossible for all sperm to swim, that mutation will be eliminated from the population because the affected individual will not produce offspring.

2. (nearly) neutral evolution, whereby mutations with (little or) no effect on the fitness of the individual may drift to high frequency by chance, or because they are linked to mutations with an effect. For example, there are hundreds of thousands of repetitive elements that invasively insert themselves throughout our genome, and generally have no observable effect on fitness, but continue to accumulate and even become fixed, simply because they do not significantly adversely affect fitness.

Whenever I hear "Survival of the Fittest", I am reminded of this quotation:

Think of how stupid the average person is, and realize half of them are stupider than that.

Thursday, April 18, 2013

So, I'm reading with the Little Bear, and we get to one of her favorites, How Do Dinosaurs Count to Ten?:

She loves naming the different dinosaurs (which, at 2 really amazes me - I had no idea how quickly kids pick up these things). We get to the page with the flying dinosaur that is labeled as a Pteranodon. I tell her it is a Pteranodon, and she responds:

"No mommy, that is a Pterodactyl."

What? First, I'm floored that she knows the word, "Pterodactyl". Second, I can clearly read that it is a "Pteranodon", but I don't know enough about dinosaurs to know if she is right, so, of course, I had to look it up.

1. There's no such creature as a "pterodactyl."

It's unclear at what point "pterodactyl" became a synonym for pterosaurs in general, and Pterodactylus and Pteranodon
in particular, but the fact remains that this is the word most people
use. Working paleontologists never refer to "pterodactyls," preferring
to focus on individual pterosaur genera.

After all this, I finally decided that, even though I have no idea when I'll read it, I should (and then did) buy the new book, My Beloved Brontosaurus, by Brian Switek, a paleontologist and science writer I recently met:

My Beloved Brontosaurus (see review here) will be waiting patiently for me on the kindle. I wonder if the Little Bear would like to read along with me?

To me, questioning the utility
of Mathematics to Science (and to Biology in particular) is like
asking why words are useful to communication.

Surely we can communicate without words? We don't really need words for
effective communication. We can easily communicate using gestures,
expressions and pictures. We can communicate frustration, joy, and
sadness without words. We can share knowledge and tell stories without
words. I’ve never understood why words are in any way related to
communicating and understanding. Words are just a tool developed to
convey information, really just an image of reality. And complex words,
specifically new vernacular as well as complicated vocabulary, these really
serve no purpose to advance understanding. Using words might describe the thoughts that we have,
but the words themselves don't actually do anything to change our
thoughts. I think I'll just keep writing until someone can prove to me
how useful words really are to communication.

Toddler Facepalm

My response to ridiculous comments is so pronounced
that that my toddler has learned to facepalm

Friday, April 12, 2013

E.O. Wilson says you can be successful as a scientist without math. Well, maybe. But, you can improve your chances of success if you take a breath, let go of your fear of math, and take some time to learn it. I think it is really quite wonderful. Oh, and if you aren't sure about where to start, there just happens to be a workshop for Mathematics in Biology. Yes, yes, go sign up!!

The workshop is intended to broaden the scientific perspective of young researchers
(primarily junior faculty, postdocs, and senior graduate students) in mathematical biology and to encourage interactions with other
scientists.

Workshop
activities include plenary talks and poster sessions, as well as group
discussions on issues relevant to mathematical biologists. Several
abstracts will be chosen
for short talks as well as poster presentations. Limited funding is available on a competitive basis.

The cartoon, the information, the presentation, are all excellent! After the awesomeness of the mantis shrimp wore off, I started thinking about how the Oatmeal, especially with this piece, is an excellent example of how to communicate science to the public.

1. Choose an intriguing title
The title, "Why the Mantis Shrimp is my new favorite animal", is both personal, curious. First of all, I don't know what a Mantis Shrimp is, so I'm curious about that. Secondly, most people have a favorite animals that is something common (e.g., dog, horse, butterfly), so it makes me want to know why this person likes a shrimp (other than they're probably delicious).

------- PART 1: Mantis shrimp thermonuclear vision -------

2. Give a clear introduction to basic science
The Oatmeal starts out with a clear introduction into basic science that most of us have probably heard sometime, but have a hard time keeping strait: Our eyes see using rods (for motion) and cones (for color).

3. Put it in perspective with something familiar
We all know dogs, and have heard either that they're color blind (they aren't), or the truth, presented here, that they have the ability to observe fewer colors than we do. Alright, I'm with you, dogs have poor color vision.

4. Relate it to humans
Oh yeah! Humans can see more colors than dogs. Woot!

5. Take small steps
Fist ask us to think a little outside the box. Whoa... butterflies have more color receptors than us... that's crazy. We can kind of wrap our brains around it. That color vision in butterflies is to us, what our color vision would be to dogs. Okay, sounds good.

6. Give the amazing punch line
Okay, with a little background about the Mantis Shrimp to familiarize us with this animal, and then the build-up. Not two, not three, not five, but sixteen color receptors!! What?!?! That is amazing. Then, following this up with some pictures of the actual animal.

------- PART 2: Mantis shrimp death machine -------

7. Play to the audience's imagination

Give us a picture of something beautiful, wonderful, but completely unrealistic in nature. Then tear that picture apart.

8. Share facts, with perspective

The appendages can snap forward as fast as a gunshot??
If humans had the same force we could throw a baseball into space??
These are things I can grasp, and I can share with friends.

9. Be entertaining
Tell a story with the science. It's okay to be a little silly (Kapow!). When communicating with the public, I think it is as important to engage your audience as it is to be accurate, or else you'll just be talking to an empty room.

Tuesday, April 9, 2013

A couple weeks ago a deep-sea researcher friend, Craig McClain, commented that one of his pet peeves is grinning cartoon octopods. He didn't give more explanation, but I'm guessing it is because it is completely anatomically incorrect to put their mouths on top of their heads (er, bodies?), and we all know that octopi rarely smile:

Smiling is forbidden (and anatomically impossible).

But, they do have a great sense of humor:

Adorable, and hilarious.

This weekend the Little Bear asked me to play with her "fish stickers", and who should be staring up at me, but a cheesin' octopus. I immediately thought of the earlier comment, and then noticed how wrong all of the pictures are (note the smiling pufferfish, and gak! starfish!!).

Cheese!

Looking across the stickers, the Little Bear was able to describe most of the species to me, and I started to wonder how harmful (although still incorrect) a cartoon octopus might be. I asked the Little Bear if she wanted to look up a video of an octopus. After an enthusiastic "yes!", we searched youTube and found some cool videos. Seriously, this one is really cool - I had NO IDEA they could just get out and walk on land, WHERE HAVE I BEEN HIDING??

Where was I? Oh yeah, cartoon, smiling, anatomically incorrect octopods. We both loved watching this videos of sea creatures, and the Little Bear had no problem identifying the octopus, or being in total awe of it. My general inclination is to always give accurate representations of life. We have a poster of real coral reef fish on her wall, we look up videos of real octopi and squid, and we try to choose books that accurately depict animals and plants. But, we can't avoid all cartoons, or stickers, or books with talking animals, and I think that's okay. The Little Bear, in my opinion, does a pretty amazing job of understanding that the smiling octopus is actually a simplification of a real octopus, and, even at 2 years old, goes back and forth between them with ease.

In a world full of cartoons, I'm happy that there are more than puppies and kitties aimed at kids. Heck, I even love the giant microbes. And really, who ever thought Chlamydia could be cute? But if these representations can help inject science into our daily lives, I'm all for them!

Yes, it would be nice if companies would make their materials realistic, especially about the natural world, which is so amazing/entertaining/intriguing on its own. But, I don't mind a few talking sharks, or smiling squids, if it increases the general public's interest of (and, hopefully, desire to understand) science. This is even more critical in areas of research that are not always immediately awesome to the public.

By the way, I showed up at daycare to find all the kids sitting and playing with finger puppets. The Little Bear had chosen a lime green octopod (which was surprisingly anatomically correct for a finger puppet - no smiling mouth here!). I guess I should ask Craig if he needs a summer intern.

Monday, April 8, 2013

I wrote this a month ago (March 5, a Tuesday), but didn't hit publish. I don't know that we ever have a typical day, but here is one day:

Wake up at 6:30am. Get the Little Bear to the bathroom (yay!), then get her dressed, and fed (homemade wheat cinnamon bread toast), and brush her teeth. Hand her off to Scott who takes her to daycare. Get myself ready, head into work.

8:00am - Start working through emails, coordinating visits, responding to messages that stacked up over night. Realize it is Scott's birthday, so hurry to call him (feeling like a schmuck), then get back to work writing some code to analyze read counts from the 1000 genome data.

12:00pm - Miller Institute lunch and lecture. Then, head back to lab and work through some results for the Rheumatoid Arthritis project, and talk to a colleague about a grant proposal he is working on.

2:30pm-ish - The phone rings. A labmate says: "Uh, Melissa... there's some guy from NBC who wants to talk to you on the lab phone." After a few seconds of mild confusion, pick up the phone. He wants to ask questions about a new manuscript (which I haven't read yet because it just came out). Super-cool! I take the next hour to carefully read through the results in question, then call back for the interview (the article is up already. Current update: This actually led to me writing up a more formal response that is under review right now.)

4:00pm - Head home to let Little Brown Dog out to do his business, and give him a short walk around the block before heading back upstairs to change, grab the jogging stroller and snacks for the Little Bear, then head out to daycare.

4:30pm - Pick up the Little Bear, and have a nice conversation on the way home. At home we made carrot muffins together, and played with Little Brown Dog. Then, while she "colored" a card for Scott's birthday (aka, poked holes in the paper, then tore it into tiny little bits), I got dinner started.

Little Bear (with her "hat") helping walk Little Brown Dog.

6:15pm - Eat dinner, then family playtime. I got to be a "tiger" that she rode around, and there was a lot of tickling involved. At one point the Little Bear (apx 30 lbs) asked me to ride her back, which was not an easy feat, let me tell you.

7:00pm - Made hot tea for me, milk for the Little Bear, then sitting together in the rocking chair and reading stories.

7:30pm - Time for pajamas, potty, and teeth-brushing (for the Little Bear). Then Scott read stories tonight and we took turns putting her to bed - asleep by 8:30ish (yay!).

9:00pm - A few hours to get some more work done, shower (maybe), and relax (?) before we start it all over again. Tonight it's peer-reviewing and working on research summary for recruiting summer undergraduate researchers.

I've recently been engaged in discussions about the ENCODE project, and, brought it up to my family and friends on facebook, asking them whether they had heard about ENCODE. Despite the splash this project has made in the scientific community, and the media coverage it got, it was my opinion that most in the general public still haven't heard about the project, let alone any of the controversy surrounding it. I thank everyone for their honest responses. I'd like to highlight my grandpa's response, which is actually the most accurate, given he's never heard of the ENCODE project. He said, verbatim:

"the word encode i think has been used since ww1 and ww2, if you mean gencode thats a new word to me. (Hi-- Melissa, papaw)" - Levi Myers

First off, he is wonderful (Hi papaw! Thank you for commenting!!). Secondly, he's totally right; the word encode is thought to have originated in apx 1919. Third, the set of people I sampled is obviously biased to my friends and family. I consider them to be a very informed and intelligent group of people who are generally interested in science and learning new things. And most of them had never heard of the ENCODE project, so here is my introduction to the project and why it is making waves in science. I meant for this to be short, but it has grown a bit, so please bear with me. And, please let me know if anything isn't clear.What is ENCODE

All of our cells contain a set of DNA, called our genome. The genome contains much of the information for building "us". Although we all have small differences in our own DNA (that make us unique!), a few years ago scientists identified the sequence of a reference human genome. This is like identifying all the pieces of a bicycle. Some bicycles are different colors, some have some slightly different pieces, but all bicycles have the same basic parts.

But, just knowing all the parts isn't enough. We need to know what all of the pieces do. ENCODE is a science project funded by the US government with the goal of understanding what all the pieces of the human genome do: to make an ENCyclopedia Of DNA Elements.

I know I said, "the good, the bad, and the ugly", but I'm going to go out of order here.

The good about ENCODE

The first part of the ENCODE project is identifying that a region has a function. This project funded a group of labs to develop a library of these functional elements that will be made freely available, and can be a resource utilized by scientists all over the world. Recently (September 2012) the labs involved with ENCODE released the phase 1 of their data, in 30 papers published in Nature (6 papers), Genome Biology (18 papers), and Genome Research (6 papers). Links to these papers can be found at the bottom of this page.

Previously we knew that 1 to 2% of the human genome codes for genes that make proteins (which do much of the work in a cell), ENCODE identified with high confidence that about 20% of the rest (noncoding) has a definable function. Many of these regions control the activity of genes. The cohort of labs working on ENCODE also identified that another 60% of the noncoding human genome may show some small signal of being functional (they call it: biochemical activity) in at least one of the tissues studied, but the function of this 60% is unknown.

They also developed (in my opinion) an funny, concise summary* of genetic research called, The Story of You, that is accessible to the general public (and narrated by Tim Minchin!!!):

*Summary up to 2:45
*Note that humans are not necessarily "more complex" than peas. Humans cannot turn sunlight into energy through photosynthesis.The ugly about ENCODE

When the huge, coordinated, 30 ENCODE papers came out, the authors made a decision to be generous in their interpretation of the word "function". So, remember up above, where I said ENCODE identified that 20% of the human genome has a known function, and another 60% has "biochemical activity", but unknown function. Well, many scientists would conservatively report that they identified 20% of the human genome is function. But, function, like any word, can have many meanings. The ENCODE group chose to define "function" to mean any biochemical activity. With this definition of function, the ENCODE authors could say that 80% (20% + 60%) is "functional".

This 80% figure was very popular among the media, and very unpopular among many scientists (see this summary by Brendan Maher, and note the comments section), with several blog responses (here is a wonderful summary, and many updates), and published responses (e.g., Graur et al, Genome Biology and Evolution, and W. Ford Doolittle, PNAS). Many of the critiques of the ENCODE project I have read focus on the hype surrounding the project, specifically how the authors chose to liberally define "function", how the journalists were uncritical of these claims, and the implications for future science and science communication. Similarly, there are, and I imagine will continue to be, discussions among scientists about whether the 80% number is "dishonest", perhaps just an "exaggeration", or a valid number to publicize. Although I'm certainly happy other people are taking this up, I have a different concern about the ENCODE project.

The bad about ENCODE

My biggest concern with the ENCODE project is that the majority of the efforts have not studied primary human tissues. The National Human Genome Research Institute website describes the cell lines, and a small bit about the rationale for choosing them for the ENCODE project here. Wait, wait, wait, what is a cell line? How is it different from primary human tissues?

Primary human tissues are basically any healthy (read, non-cancerous) tissue that we could sample from your body (for example, cheek cells, or blood cells, or brain cells, or liver cells). Why don't we just study these primary tissues, you might wonder? Well, with current technology, it is very difficult to get these cells to survive long outside of the body. There are whole labs dedicated to learning how to grow and sustain primary human tissues.

If we can't use primary human tissues because they die too quickly, what can we use? We can use cell lines. Cell lines are "immortal" cells that are derived from primary human tissues, but have some mutations (either natural, like the HeLa cells you may have heard of), or induced, that allow them to continue to grow and reproduce outside of a human body. These cell lines have helped scientists make many advances, including studying the effects of viruses on human cells, notably in developing vaccines, including the polio vaccine, and in studying cancer and cancer treatments.

But, cell lines are not healthy primary human tissues. The aspect of these cell lines that makes them useful for research (that they continue to replicate outside of the body), also means that they likely have differences in their DNA from primary human tissues. In fact, ENCODE notes:

"Effort was also made to select at least some cell types that have a relatively normal karyotype."

The DNA in each of our cells gets wound up into chromosomes. The "karyotype" refers to the number and structure of these chromosomes.

Normal human male karyotype (22 autosomes + X + Y)

Cell lines often have karyotypes that are not the same as primary human tissues. Human cells have 46 chromosomes (23 pairs, see above), but cell lines may have more, or the chromosomes may have unusual structures.

Thus, while these cell lines are derived from human tissues, they behave in unusual ways, and their DNA has unusual structure. Given these differences, I wonder how reasonable it is to assume that the fine-scale DNA patterns and functions identified in cell lines will actually mimic healthy human tissues.

Friday, April 5, 2013

Without arms, emu hug with their minds, or I like to think that they do.

Like mammals, sex is determined in birds using sex chromosomes, but in birds it is a little different. In mammals (dogs, humans, cows) females have two copies of the same sex chromosome (XX), and males have one X, and one Y, where genes on the Y chromosome turn on the pathways for male features. In birds, it is the males who have two copies of the same sex chromosome (here we call them ZZ), and females who have one Z chromosome and one W chromosome. In birds, male-specific features require expression (product) from two copies of a gene (so males have two Z chromosomes).

W and Y are usually much smaller than their partners

What you'll notice in the picture above is that in both mammals and birds one of the sex chromosomes (X or Z) is large, while the other (Y or W) is small. Generally one of the sex chromosomes becomes sex-specific (such as the Y passed down through the male lineage in mammals, or the W passed through the female lineage in birds). As this chromosome becomes sex-specific, it will accumulate genes, and functions, that are beneficial to one sex, and neutral, or even harmful to the other. Usually all chromosome pairs can swap bits of DNA (also called recombination), but to prevent these sex-specific genes from acting in the opposite sex (where they would do harm), the sex chromosomes usually stop swapping DNA. But, these swaps between partners can also serve as a bandage to fix errors that happen (think, having a partner to remove that broccoli you didn't know was lodged in your teeth, but instead of broccoli, it is an error in a gene). A drawback of stopping the swaps is that without a partner to check and make sure everything is working properly, the W and Y chromosomes start accumulating mutations, losing genes, and shrinking.

But, when Vicoso, Kaiser and Bachtrog looked at the emu sex chromosomes, they saw something really amazing. Whereas the W in most birds is small and degraded (like the human Y), the W in emu is quite large, nearly the same size as it's partner.

Emu W has nothing to prove to you.

This is pretty unusual among bird sex chromosomes, and the authors wanted to figure out why. So, they looked at how the genes on the sex chromosomes were working in males and females. Although sometimes we think of genes as being "on" or "off", in reality many genes are "on", but they are doing their jobs (making proteins) with a higher or lower efficiency (think of your heart; if it were ever truly "off" you'd be dead, but there are times when your heart is pumping slowly, and times when it is racing, and it is the level at which your heart is working that is important). So, looking at genes on the emu Z and W, they saw that many of the genes were being used at much higher levels in males than in females. This suggests that there is some mechanism by which genes on the emu sex chromosomes have evolved to favor functions in males over females, which side-steps the usual path of sex chromosome evolution that would lead to a small, degraded W. Well-played, emu, well-played.

Thursday, April 4, 2013

We've been trying to introduce a variety of foods and cultures to the Little Bear. A few weeks ago I made some eggplant stir-fry with rice, and let the Little Bear test out some chopsticks.

I was wondering about eggplants, so decided to look them up. Diversity (genetic differences) among eggplants in three regions (Sri Lanka, China, and Spain) was recently studied by Maria Hurtado and colleagues. Both the physical differences and the genetic differences were highest among the Sri Lankan eggplants, which suggests that they are closer to the location of the founder population, than either the Chinese or Spanish eggplants. Curiously, physical and genetic diversity were also quite high among the Chinese and Spanish eggplants, with very little physical and genetic diversity shared across eggplants from all three regions.

Wow! That's a lot of diversity!

Thus, it seems like eggplants originated somewhere near the region occupied by modern India, but quickly spread North, going both East, and West.

Interestingly, the authors state in their conclusion that differential selection acting on the three populations accounts for the differences observed between them:

At the morphological level, a clear differentiation exists among the different origins, indicating that different selection criteria have been applied in each secondary center of diversity, leading to a typical syndrome of traits for each origin.

While selection (particularly artificial human selection for specific traits) may be acting, it is also possible that much of the differences are simply due the diversity that happened to be present in the subset of eggplants that were taken and cultivated in each area. Or, the eggplants in the different regions were cultivated in a short time span from the founder population, then we might expect diversity to be quite high in all populations, without needing to invoke selection. The observed differences may merely represent neutral variation. It would be interesting to see a test for this.

Oh yeah, I was talking about chopsticks. The chopsticks went over pretty well, and the eggplant was delicious. A win with everyone:

Wednesday, April 3, 2013

While visiting NESCent in North Carolina, we stopped in for some LocoPops. The popsicles were delicious (I had cookies and cream). I definitely recommend checking it out if you ever visit Durham. While there I stopped into the restroom and was super-excited to see the tiny potty attachment. Way to be family-friendly LocoPops!

Tuesday, April 2, 2013

I had lunch with a group of Miller Fellows, and the Director of the Miller Executive Committee, Professor Jasper Rine. We talked about a lot of things, but the discussion kept coming back to topics related to applying for research faculty positions, and the two body problem. Here's my summary of the key points:

Be forthright about the two-body problem.

Jasper has sat on several search committees, and it is his suggestion that, if there is a two-body problem (i.e., that two people are seeking academic, or professional positions, in the same physical location), it is best, as an applicant, to mention this up-front in the cover letter.

But, what if the search committee doesn't want to deal with two-body problem?

Search committees are concerned with finding the best applicant for the position and for their department, fullstop. The search committee will be interested in hiring you because of your academic record, the likelihood that you will collaborate well with the people in the department, and the expectation that you will be a productive faculty member. Search committees are also aware that many researchers will have partners who are also researchers. If the fact that you have a partner who will also require a position will negatively affect their decision to invite you for an interview, or to hire you, then the climate in that department will likely also reflect this. Or, more simply, if the department won't hire you simply because it might be difficult to find your partner a position, you probably don't want to go there anyway.

Okay, so they will hire me, even knowing about this other body. But why bring it up early?

I hadn't thought of this before, but Jasper pointed out that all departments have to work within a bureaucratic framework. What this means is, the sooner they know that they may have to work to find a position for two people, instead of one, the sooner they can get the paperwork rolling, the sooner they can seek out funding for an additional position, and the sooner they can contact other departments, and even other universities, about potential positions for your partner.

Sometimes the two-body "problem" can end up being an advantage.

Admittedly, the highest tier of Universities knows that they don't have to negotiate to get great people (and despite what you've heard about the benefits of multiple offers, some Institutions won't negotiate at all). But let's take a quarter-step back, and consider the excellent research institutions across the country that may not be located in the "ideal" locations (be it rural, or isolated with respect to other job opportunities, or in direct competition with the top-tier institutions, or very urban, who knows), or that have a higher teaching load, or, that may recruit fewer or no graduate students. These institutions understand that it is to their recruitment advantage to be able to offer two positions, and they can "steal" you away from another institution that is unwilling to negotiate these kinds of positions. Second, and more importantly, if you and your partner are both excellent applicants, it can be a direct advantage to the University to hire two highly-qualified candidates.

So, while the two-body problem is stressful, and requires cooperation from all sides, many institutions understand and value the benefits of dual-academic couples. (Please someone remind me of this in a few months.)

In mammals, sex is determined using chromosomes, where two X chromosomes (XX) generally results in the formation of an anatomical female, and one X and one Y chromosome (XY) generally results in the formation of an anatomical male.

There is, however, a family (as in family, genus, species) of rats called Echimyidae, or spiny rats, that have sex chromosomes that don't fit the normal mammal mold.

There is a lot to talk about with these rats, but I'll focus on the recent paper, detailed at the bottom, who study a smaller subset of the spiny rats, a genus called Proechimys, that lives in the Amazon forrest. Generally mammals have an even number of total chromosomes, one half coming from the mother, and one half coming from the father (for example, humans have 2n=46 chromosomes) In these rats, however, the researchers noticed that all of the females had full complement (2n) of 16 chromosomes, but that males had 17 chromosomes! After more investigation they realized that this incongruence happened because there was an addition to the sex chromosomes (X and Y) that had fused to the X chromosome, but had not fused to the Y. This means that the X chromosome in these rats is quite large, and that females have two of these large X chromosomes, but males have one large X chromosome and two Y chromosomes:

So, females have 14 autosomes (non-sex chromosomes) and two X chromosomes (for a total of 16) and males have 14 autosomes, one X, and two Y's (for a total of 17). This kind of addition to the sex chromosomes has happened, and will continue to happen in many species. It even happened in humans (the region was fused to both the X and the Y). Because the Y chromosome is constantly degenerating, these additions may serve to give more raw material to the Y, prolonging its life. I am excited to see what we'll find out as technology give us the opportunity to learn about the genetics of more and more species.

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